Lipids, such as triglycerides and cholesterol, are transported through the blood in lipoproteins. Both overproduction and underutilization of lipoproteins can lead to hyperlipoproteinemia and atherosclerosis. Lipoprotein lipase (LPL) is an enzyme which catalyzes the hydrolysis of lipoprotein triglycerides. LPL participates in the first steps of lipoprotein breakdown. Because of serious methodologic problems there are many unanswered questions about the importance of LPL in the hyperlipidemias of man. The broad issue of this research project is how endocrine, metabolic and genetic factors influence lipoprotein lipase and how these factors relate to catabolism of lipoproteins in man. Our program entails: 1) Studies of the immunology, morphologic localization and other basic characteristics of the lipoprotein triglyceride hydrolases. 2) Studies of tissue triglyceride hydrolase activities in experimental animals to define the influences of aging, nutrition, endocrine milieu, drug therapy and disease. 3) Studies of laboratory methods to develop more effective methods for the measurement of LPL. 4) Clinical studies of triglyceride hydrolase activities in patients in whom defective lipoprotein removal mechanisms may contribute to the pathogenesis of hyperlipoproteinemia. We will emphasize clinical research related to the physiological role of lipoprotein lipase in man. Experimental animals will be used to supplement these studies, particularly for the measurement of tissue lipoprotein lipase levels. Biochemical investigations will be continued as they relate directly to our understanding of role of lipoprotein lipase in human illness and to the techniques for its study. BIBLIOGRAPHIC REFERENCES: Ence, T.J., Wilson, D.E., Flowers, C.M., Chen, A.L., Glad, B.W. and Hershgold, E.J. Heparin metabolism and heparin-released triglyceride lipase activity during long-term estrogen progestin treatment. Metabolism, February, 1976. Bagdade, J., Wilson, D.E. and Shafrir, E. Mechanism of hyperlipidemia in chronic uremia. Clin. Res., 1976.